TY - JOUR
T1 - Treatment of ear and bone disease in the Phex mouse mutant with dietary supplementation
AU - Wick, Cameron C.
AU - Lin, Sharon J.
AU - Yu, Heping
AU - Megerian, Cliff A.
AU - Zheng, Qing Yin
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Hypothesis Phosphorus and vitamin D (calcitriol) supplementation in the Phex mouse, a murine model for endolymphatic hydrops (ELH), will improve otic capsule mineralization and secondarily ameliorate the postnatal development of ELH and sensorineural hearing loss (SNHL). Background Male Phex mice have X-linked hypophosphatemic rickets (XLH), which includes osteomalacia of the otic capsule. The treatment for XLH is supplementation with phosphorus and calcitriol. The effect of this treatment has never been studied on otic capsule bone and it is unclear if improving the otic capsule bone could impact the mice's postnatal development of ELH and SNHL. Methods Four cohorts were studied: 1) wild-type control, 2) Phex control, 3) Phex prevention, and 4) Phex rescue. The control groups were not given any dietary supplementation. The Phex prevention group was supplemented with phosphorus added to its drinking water and intraperitoneal calcitriol from postnatal day (P) 7–P40. The Phex rescue group was also supplemented with phosphorus and calcium but only from P20 to P40. At P40, all mice underwent auditory brainstem response (ABR) testing, serum analysis, and temporal bone histologic analysis. Primary outcome was otic capsule mineralization. Secondary outcomes were degree of SNHL and presence ELH. Results Both treatment groups had markedly improved otic capsule mineralization with less osteoid deposition. The improved otic capsule mineralized did not prevent the development of ELH or SNHL. Conclusion Supplementation with phosphorus and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.
AB - Hypothesis Phosphorus and vitamin D (calcitriol) supplementation in the Phex mouse, a murine model for endolymphatic hydrops (ELH), will improve otic capsule mineralization and secondarily ameliorate the postnatal development of ELH and sensorineural hearing loss (SNHL). Background Male Phex mice have X-linked hypophosphatemic rickets (XLH), which includes osteomalacia of the otic capsule. The treatment for XLH is supplementation with phosphorus and calcitriol. The effect of this treatment has never been studied on otic capsule bone and it is unclear if improving the otic capsule bone could impact the mice's postnatal development of ELH and SNHL. Methods Four cohorts were studied: 1) wild-type control, 2) Phex control, 3) Phex prevention, and 4) Phex rescue. The control groups were not given any dietary supplementation. The Phex prevention group was supplemented with phosphorus added to its drinking water and intraperitoneal calcitriol from postnatal day (P) 7–P40. The Phex rescue group was also supplemented with phosphorus and calcium but only from P20 to P40. At P40, all mice underwent auditory brainstem response (ABR) testing, serum analysis, and temporal bone histologic analysis. Primary outcome was otic capsule mineralization. Secondary outcomes were degree of SNHL and presence ELH. Results Both treatment groups had markedly improved otic capsule mineralization with less osteoid deposition. The improved otic capsule mineralized did not prevent the development of ELH or SNHL. Conclusion Supplementation with phosphorus and calcitriol improves otic capsule bone morphology in the Phex male mouse but does not alter development of ELH or SNHL.
UR - http://www.scopus.com/inward/record.url?scp=84990840614&partnerID=8YFLogxK
U2 - 10.1016/j.amjoto.2016.09.014
DO - 10.1016/j.amjoto.2016.09.014
M3 - Article
C2 - 27733274
AN - SCOPUS:84990840614
SN - 0196-0709
VL - 38
SP - 44
EP - 51
JO - American Journal of Otolaryngology - Head and Neck Medicine and Surgery
JF - American Journal of Otolaryngology - Head and Neck Medicine and Surgery
IS - 1
ER -